title: Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects.
abstract: The direct targets of extremely low and microwave frequency range electromagnetic fields (EMFs) in producing non-thermal effects have not been clearly established. However, studies in the literature, reviewed here, provide substantial support for such direct targets. Twenty-three studies have shown that voltage-gated calcium channels (VGCCs) produce these and other EMF effects, such that the L-type or other VGCC blockers block or greatly lower diverse EMF effects. Furthermore, the voltage-gated properties of these channels may provide biophysically plausible mechanisms for EMF biological effects. Downstream responses of such EMF exposures may be mediated through Ca(2+) /calmodulin stimulation of nitric oxide synthesis. Potentially, physiological/therapeutic responses may be largely as a result of nitric oxide-cGMP-protein kinase G pathway stimulation. A well-studied example of such an apparent therapeutic response, EMF stimulation of bone growth, appears to work along this pathway. However, pathophysiological responses to EMFs may be as a result of nitric oxide-peroxynitrite-oxidative stress pathway of action. A single such well-documented example, EMF induction of DNA single-strand breaks in cells, as measured by alkaline comet assays, is reviewed here. Such single-strand breaks are known to be produced through the action of this pathway. Data on the mechanism of EMF induction of such breaks are limited; what data are available support this proposed mechanism. Other Ca(2+) -mediated regulatory changes, independent of nitric oxide, may also have roles. This article reviews, then, a substantially supported set of targets, VGCCs, whose stimulation produces non-thermal EMF responses by humans/higher animals with downstream effects involving Ca(2+) /calmodulin-dependent nitric oxide increases, which may explain therapeutic and pathophysiological effects.
authors.affiliation: Professor Emeritus of Biochemistry and Basic Medical Sciences, Washington State University, Portland, OR, USA. martin_pall@wsu.edu
authors.forename: Martin L
authors.initials: ML
authors.lastname: Pall
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D053904:DNA Breaks, Single-Stranded; D004574:Electromagnetic Fields; D006801:Humans; D015640:Ion Channel Gating; D010012:Osteogenesis / Q000502:physiology; D015398:Signal Transduction
chemical_list: D015220:Calcium Channels
keywords: calcium channel blockers; intracellular Ca2+; low frequency electromagnetic field exposure; nitric oxide; oxidative stress; voltage-gated calcium channels